The marrow was needed to test a tantalizing hypothesis: that Scios' experimental rheumatoid arthritis pill, SCIO-469, might also treat cancer. As Crockett, manager of the company's drug projects, delivered the bone marrow to Scios researchers in February 2003, he knew there was more at stake than product development.
His boss, Scios Chief Executive Richard B. Brewer, 54, donated the marrow. Brewer had multiple myeloma, an incurable blood cancer that might be helped by the company's pill.
The theory at the company, which is now based in Fremont, was that the drug might prevent malignant cells from multiplying, maybe one day turning myeloma into a manageable illness, like diabetes.
But scientists had to work fast. The company's board of directors was preparing to sell the unprofitable biotech to drug giant Johnson & Johnson. And there were no guarantees that the SCIO-469 cancer project would continue under new ownership. J&J saw enormous potential in SCIOS-469 perhaps a billion dollars a year but as a pill for rheumatoid arthritis patients.
Brewer hoped to persuade his new bosses to also test the pill in cancer. Most of the drugs he had used to treat his cancer were old and harsh; one chemo drug had wiped out all feeling in Brewer's feet. He became ill and
"I'm hoping (patients) won't have to go through what I went through," said Brewer, who became Scios CEO in 1998 after rising through the ranks at South San Francisco biotechnology giant Genentech Inc.
Those at Scios who had watched Brewer battle his illness believed they were on a mission.
"When someone you know and respect gets a disease, you get angry," said Scios' top scientist, George F. Schreiner. "We hated myeloma. ... We wanted to tear it down, plow it under the ground and put enough salt in so it never comes back."
A top priority at Scios from the Greek word "Scionoso" meaning "to know" was developing a drug to neutralize p38, an enzyme believed to spur inflammation in rheumatoid arthritis patients. There were few effective drugs for the joint disease, which affected 1 million Americans, making it a lucrative market.
Using sophisticated computer programs, Scios researchers designed molecules that looked like they might block the activity of p38, and neutralize it. Guided by the computer models, chemists then mixed one compound after another in search of a usable drug.
As Scios scientists closed in on their goal, they began to hear the footsteps of big pharmaceutical companies working on similar pills. Every day there were rumors that a bigger competitor had leaped ahead. Then, just as suddenly, GlaxoSmithKline, Merck & Co. and others had setbacks, leaving Scios in the lead.
By the end of 2000, Scios was ready to test its pill in patients with rheumatoid arthritis.
Meanwhile, Brewer faced his own struggle. The first sign of trouble came in May 2000, when Brewer felt a twinge in his back. At first, he thought he had strained a muscle when he loaded his dog, a 70-pound boxer, into the back of his SUV. But the pain worsened, so Brewer went to a doctor, who told him he had a compressed disk.
His condition didn't improve with rest. By spring 2001, Brewer could not stand upright and had to sleep in a chair to avoid intense pain.
Brewer kept up a grueling schedule, which was also taking its toll. The company was on the verge of receiving long-awaited federal approval of its first product an intravenous medicine for congestive heart failure patients and important meetings were scheduled with the Food and Drug Administration.
Brewer steadily lost weight and the pain got worse, despite visits to a chiropractor. Aspirin didn't help. Damage to his spine had shaved an inch off his 6-foot 4-inch height.
The scientists on Scios' executive team were alarmed by their boss' worsening condition. Chief medical officer Darlene Horton, a physician, feared she was watching Brewer die. She warned him that he might have cancer.
"This is not normal back pain," Horton recalled telling him. "You don't need massages, you don't need a chiropractor. You need an MRI now." But Brewer told her his bone scans, another sort of imaging test, showed no sign of disease.
Finally, at the recommendation of his doctor, Brewer had a surgeon inject plastic into his spine to cushion the damaged disk. During the procedure, the surgeon took a bone marrow biopsy.
Driving to work days later, Brewer took a call from his doctor on his cell phone. The executive learned he had myeloma, a cancer he had never heard of. The disease destroys plasma cells, which produce antibodies and are found in bone marrow, the soft tissue inside bones. Nearly two-thirds of Brewer's marrow was malignant. Without treatment, he would be dead in a year.
In late summer 2001, Brewer started high doses of chemotherapy at City of Hope National Medical Center in Duarte. Every two weeks, doctors loaded drugs into his body through a catheter implanted in his chest. He lost weight and went bald.
Six months later, he underwent a risky bone marrow transplant to restore damaged tissue. Brewer recalled long days in his hospital bed, wired to pumps and monitors, too sick and exhausted to watch TV. He marked time by observing shadows march across his room as the sunlight in his window faded.
"It was the worst experience I could have imagined," he said. "Every cell in your body has been turned upside down and backwards. It changes you."
Brewer was back at work in April 2002. His cancer was in remission, but because myeloma is incurable, Brewer did not know how long he would remain cancer-free. His doctor at City of Hope, Stephen Forman, said remissions could last more than five years, or as little as one.
Although tired and thin, Brewer plunged into looking for a deep-pocketed drug company to help Scios develop its arthritis pill. Large clinical trials needed to test arthritis drugs were expensive, and the small company did not have the resources to complete the work on its own.
Through the spring and fall, big drug companies came calling. Brewer had hoped to license rights to the pill, but negotiations took a sharp turn. By mid-December, two companies, including Johnson & Johnson, said they wanted to buy Scios. With Scios' permission, the suitors started reviewing confidential documents in preparation for a bid.
Then, in January 2003, Brewer spotted an article in a newsletter about a study that linked the p38 enzyme the target of SCIO-469 to myeloma. The researcher was Kenneth Anderson of the Dana-Farber Cancer Institute in Boston, an authority on the disease.
Brewer contacted Anderson, who was surprised by the call. He was used to hearing from industry scientists but seldom talked shop with CEOs. He explained to Brewer that p38 releases chemicals that spur the growth of cancerous myeloma cells. In theory, if a drug blocks p38, the tumor can't survive. Brewer turned the article over to one of his top researchers, Linda Higgins, and asked her to dig deeper. The assignment made her nervous at first.
"I was worried I would have to deliver disappointing or equivocal news," she said. "There was nothing in the literature connecting these dots except Ken Anderson's work."
But after a week of intense research, Higgins told her boss: "I think we have a shot."
Elated, Brewer told his wife, Debbie. The couple, now divorced, had struggled to find a meaning in Brewer's illness. Brewer had immersed himself in books about spirituality and healing, and at one point consulted what he called a "life coach." All the while, a potential treatment for Brewer's illness was in his company's lab.
"My God, Dick," Debbie told him, becoming tearful as she recalled the moment. "Maybe this was why. You were meant to develop this drug."
Brewer shared her sense of destiny. If successful, SCIO-469 might help patients like himself while sparing them chemotherapy treatments.
"It was providential," Brewer said. "Unless you believe that things just happen randomly but I don't."
Higgins needed healthy cells from human bone marrow for her experiments, so Brewer volunteered. The first anniversary of Brewer's bone marrow transplant was approaching, and he was scheduled for a full day of medical tests at City of Hope. The CEO arranged to have marrow taken for Scios at the hospital.
In early February 2003, as acquisition talks heated up, Brewer went to City of Hope, accompanied by Crockett, who toted the red-and-white cooler. Brewer's wife and son also made the trip. As the CEO waited between tests, he worked his cell phone, trading calls with lawyers and Scios directors about J&J, which had become the front-runner. Then, during a physical exam, a physician used a long needle to extract marrow from Brewer's pelvic bone. He squeezed some of the pinkish tissue into a vial and packed it in the ice-filled cooler.
A short time later, just past 6 p.m., Brewer emerged from the examination room and handed the cooler containing his marrow to Crockett.
Before leaving the hospital, Brewer received welcome news: His cancer had not returned. Brewer, his family and Crockett had a celebratory steak dinner at a nearby restaurant, and, because it was late, spent the night at a hotel. The cooler never left Crockett's side. It was under his feet as he dined and near his bed as he slept.
Early the next morning, they flew aboard a private jet from Burbank to San Francisco. A driver whisked Crockett from the airport to Scios, where Higgins was waiting for him. It was about 9 a.m.
Because cells begin to die as soon as they leave the body, Higgins had to work quickly. "We were stretching the envelope," she said.
Higgins isolated very specific cells, called stromal cells, from Brewer's tissue. In healthy people, stromal cells form the scaffolding that supports the blood-forming cells in the marrow. In patients with myeloma, stromal cells become "brainwashed" by cancerous plasma cells to produce nourishing chemicals, called cytokines.
While stromal cells do the bidding of cancer cells, they remain healthy and don't become malignant.
Under a microscope, Brewer's cells were translucent specks against a background of pale yellow and pink. They looked healthy good news, because Higgins needed to incubate them so she would have many cells available to test SCIO-469.
Higgins took a photograph of the cells and e-mailed a copy to Brewer because she knew he would want to see them.
"It was eerie," he recalled. "I had never seen my cells before. And to think they had been attacked . . . "
Brewer and Higgins code-named the cells 103TK, a twist on the tail number of the CEO's private aircraft. Higgins didn't want her team to have the added pressure of knowing they were experimenting on the boss' tissue.
Four days after his trip to City of Hope, Brewer voted with the rest of Scios' directors to accept a $2.4-billion offer for the company from J&J.
Brewer had not wanted to sell the company. Scios, after a decade of disappointment and recent layoffs, had finally tasted success. Its heart drug had been approved, and the company appeared close to potential breakthroughs in arthritis and cancer. But as a director accountable to shareholders, Brewer said he could not turn down J&J's offer.
During negotiations with J&J, Brewer made a case for continuing the myeloma project after the merger. To J&J pharmaceutical group president Joseph Scodari, the research sounded plausible, but sketchy. "It was obvious to us that Dick not only saw this as a business opportunity but had a great personal interest in this," he recalled.
Brewer knew the transition to new ownership would take several months, time Scios could use to build a case for the drug. "We decided to go full blast," Brewer said.
One of his first steps was to recruit expert advisers, including Anderson of the Dana-Farber institute. Anderson flew to California in late February and came away impressed with the small company's science and inspired by its CEO.
"The circumstances that brought us together were very rare," Anderson said. "One has to believe there must be a reason."
Still, many at Scios worried about scientists at the company losing objectivity on a project so dear to them and their CEO. So the myeloma team held open forums, allowing other scientists to grill them. Brewer resolved to stay out of his scientists' way. "I didn't want anyone feeling guilty that if they didn't do something, the CEO was going to be unhappy," he said.
Higgins wrote a detailed plan to test SCIO-469. She coaxed the healthy stromal cells from Brewer's marrow to secrete the chemicals that fed tumors. Then she added SCIO-469 to the mix. With a team of junior scientists, Higgins repeated each step three times with the same encouraging result: The flow of nourishing chemicals slowed.
Much work remained before the pill would be ready to test in cancer patients.
Higgins' team worked late, often past 9 p.m. It wasn't unusual for Higgins to arrive in her lab at 3:30 a.m. on Sundays; she put in a few hours before going home for breakfast with her two preteen children.
"At the end of every day, seven days a week, I'd ask myself the same question: Why can't I go faster?" she said.
Brewer touted the project at every opportunity. "Dick really kept J&J focused on myeloma as something worth pursuing," said Crockett, who attended integration meetings. "They all knew Dick's situation, but we weren't doing it just because Dick had the disease. We had experts telling us to continue."
At a gathering of top J&J executives in Orlando, Fla., in May 2003 Brewer outlined all of Scios' drug development projects. Included were data generated by Higgins' team. The studies impressed J&J, which allocated funds to continue the experiments.
"The science made sense and the business opportunity was significant," Scodari said later.
By mid-June 2003, Higgins completed her work. Thirty people Scios scientists, their academic advisers and representatives of J&J gathered at a hotel in Half Moon Bay to review all the data. Higgins told the group that myeloma cells in a lab dish became weaker when SCIO-469 was added. The healthy stromal cells were unharmed.
At one point, Crockett drew the room shades and shut out the ocean view to keep the group focused. Higgins' work suggested that long-term use of SCIO-469 would lead to the death of myeloma cells. At the very least, the experts believed, the pill would spare patients the severe bone pain and damage that Brewer had experienced.
By the end of the meeting, the experts had devised a plan for testing SCIO-469 in cancer patients. "That is when our p38 inhibitor became a full development oncology project," Crockett said.
Today, three years after his bone marrow transplant, Brewer remains in remission. He is fortunate. Statistics show that more than half of myeloma patients are dead within five years of diagnosis.
Brewer is not in the clear, however, and his treatments haven't ended: He receives regular infusions of a drug to rebuild his bones.
Brewer resigned from Scios in February, in a mock graduation ceremony at the company's Fremont headquarters. A large screen in the auditorium flashed photos of his dog, his family and Brewer, first as a businessman, then as a patient tethered to an intravenous line.
"What I am hoping is that patients will be able to take two pills a day and live with their cancer," Brewer said. "That would be Valhalla for us."